Mannose-binding lectin codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit

Objective.?Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Invasive fungal infections are associated with significant morbidity and mortality among preterm infants cared for in the neonatal intensive care unit (NICU). Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the presence of any association between MBL gene polymorphism and nosocomial invasive fungal infection in preterm neonates.

Methods.?Codon 54 (B allele) polymorphism in exon 1 of the MBL gene was investigated in 31 patients diagnosed as nosocomial invasive fungal infection and 30 control preterm neonates.

Results.?AB genotype was determined in 26% and 30% of patient and control groups, respectively, and the difference was not statistically significant. AA genotype was determined in 74% of the patient group and in 67% of the control group, and the difference was not statistically significant. B allele frequency was not different significantly in the patient group (13%) compared to the control group (18%).

Conclusions.?In our study, no relationship was found between MBL codon 54 gene polymorphism and the risk of nosocomial invasive fungal infection in preterm neonates in NICU.     

Altered distribution of mannose-binding lectin alleles at exon I codon 54 in women with vulvar vestibulitis syndrome

OBJECTIVES: Mannose-binding lectin (MBL) is active in the innate immune defense against microorganisms. In this study, we determined whether vulvar vestibulitis syndrome, a disorder of unknown etiology, was associated with an altered distribution of MBL alleles. STUDY DESIGN: Buccal swabs were obtained from women with vulvar vestibulitis syndrome in New York (62) and from 2 cities in Sweden (60), as well as control women in New York (48) and Sweden (51). DNA was tested for a single nucleotide polymorphism at codon 54 in exon I by polymerase chain reaction, endonuclease digestion, and gel electrophoresis. Blood samples were also obtained from the New York women and tested by ELISA for plasma MBL concentrations. The relationships between genotype, allele frequencies, blood MBL levels, and diagnosis were analyzed by Fisher exact test and one-way analysis of variance. RESULTS: The variant MBL allele, MBL*B, was detected in 35.5% and 26.7% of vulvar vestibulitis patients from New York and Sweden, respectively. Only 12.5% of New York controls (P=.007) and 9.8% of Swedish controls (P=.01) were MBL*2-positive. All women, with one exception, who were positive for MBL*B were MBL*A/MBL*B heterozygotes. Women who carried MBL*B had almost a 10-fold reduction in median plasma MBL concentrations (278 ng/mL), as opposed to women who were MBL*A homozygotes (1980 ng/mL) (P < .0001). CONCLUSION: MBL*B carriage and reduced plasma MBL levels are more common in women with vulvar vestibulitis syndrome than in control patients, and may contribute to symptomatology in a subset of patients.     

Mannose-binding lectin serum levels in neonatal sepsis and septic shock

Objective.?To evaluate mannose-binding lectin (MBL) serum levels as a marker for predicting sepsis, septic shock, and their outcomes in neonates.

Patients and methods.?A prospective study was conducted on 62 neonates (27 preterm and 35 full term) with culture-proven sepsis and 35 controls. Serum levels of MBL were measured by immunoassay.

Results.?Of 62 infants with positive blood cultures (Gram-negative?=?44 and Gram-positive?=?18), 11 infants had severe sepsis and 6 neonates developed septic shock. MBL levels were significantly lower in infants with sepsis than in control group (0.39?±?0.07 vs. 1.34?±?0.03 μg/ml; p?<?0.001). The lowest MBL levels were detected in those infants with septic shock, particularly those who died (p?<?0.05). MBL had high sensitivity (96.7), specificity (97.1), positive (98.3), and negative (94.4) predictive values to detect sepsis.

Conclusion.?Low MBL serum levels could be considered as sensitive and specific marker for predicting sepsis, septic shock, and their clinical outcomes in newborn infants.     

Fertility preserving options in patients with gynecologic malignancies

A proportion of reproductive age women are affected by gynecologic malignancies. This patient population is faced with difficult decisions, related to their cancer care and treatment, as well as future childbearing potential. Therefore, it is important for gynecologists to be familiar with fertility sparing management options in patients with cervical, ovarian, and endometrial cancer. In addition to understanding the surgical approaches available, providers should be able to counsel patients regarding their eligibility for and the indications and limitations of fertility sparing therapy for gynecologic cancer, allowing for appropriate referrals. A comprehensive PUBMED literature search was conducted using the key words "fertility preservation," "cervical cancer," "endometrial cancer," "ovarian cancer," "borderline tumor of the ovary," "germ cell tumor," "obstetrical outcomes," "chemotherapy," and "radiation." The following review summarizes fertility sparing options for patients with cervical, ovarian and endometrial cancer, with an emphasis on appropriate patient selection, oncologic, and obstetric outcomes.     

Association of TP53 codon 72 polymorphism with susceptibility to ovarian carcinomas in Serbian women

Objectives

Finding a potential genetic factor associated with a deadly disease, such as ovarian carcinoma, is of particular importance. The aim of this study was to examine the role of the TP53 codon 72 polymorphism in ovarian carcinoma development in Serbian women.

Study design

47 wild-type TP53 gene ovarian carcinoma samples and 70 cervical smears from gynecologically healthy women were analyzed. DNA was extracted by a salting-out procedure. Codon 72 polymorphism was assessed by PCR-RFLP method. χ², Fisher exact test and odds ratio were used for statistical analysis.

Results

The distribution of Arg/Arg, Arg/Pro and Pro/Pro genotypes of codon 72 of the TP53 gene was: 46.8%, 46.8% and 6.4%, respectively in the ovarian carcinomas and 64.3%, 31.4% and 4.3%, respectively in the control group. We observed an increased risk for the development of ovarian carcinoma for Pro homozygotes in relation to heterozygotes plus Arg homozygotes (OR = 1.52; 95% CI 0.29–7.89) and a higher one for Pro/Pro plus Arg/Pro genotype in relation to Arg homozygotes (OR = 2.04; 95% CI 0.96–4.34).

Conclusion

The results showed no association between codon 72 TP53 gene polymorphism and risk for development of ovarian carcinoma in Serbian women. However, this observation requires further analysis of a larger case–control study group.     

Fertility considerations in young women with hematological malignancies

The need for practice guidelines for fertility preservation in young women with hematological malignancies has been increased. To develop recommendations, publications relevant to fertility preservation and hematological cancers were identified through a PubMed database search and reviewed systematically, focusing on the effects of oncological treatments on fertility as well as on the efficacy, feasibility and risks of existing fertility preservation methods.     

Genetic polymorphisms as predictive and prognostic biomarkers in gynecological cancers: a systematic review

Purpose

Numerous studies have explored the potential role of genetic polymorphisms as predictive or prognostic biomarkers in gynecologic malignancies. A systematic review for all eligible polymorphisms has not yet been reported. The aim of this study was to summarize the current status of the field and provide direction for future research.

Design

We searched literature databases (MEDLINE, EMBASE, Cochrane) from 2006 to April 2011 to identify studies evaluating the association between gene polymorphisms and clinical outcome in ovarian, endometrial, cervical, or vulvar cancer. The main outcome measures were overall survival (OS) and progression-free survival (PFS). Studies reporting relationships between polymorphisms and toxicity were also included.

Results

Sixty two studies met the inclusion criteria. The median sample size was 140. Most of the included studies (n = 50, 81%) were conducted in ovarian cancer patients. Almost a third assessed potential predictive associations between gene polymorphism and outcome in ovarian cancer. The most commonly evaluated genes were ERCC1, VEGF, ABCB1 (MDR), and GSTP1. Most studies (n = 44, 71%) were observational case-series. Only four studies (6%) included a validation arm and patient population ethnicity was explicitly stated only in 27% of included studies.

Conclusion

No consistent association between any gene polymorphism and clinical outcome in gynecological cancers has been found across studies. There is incomplete adherence to the REMARK guidelines and inadequate methodology reporting in most studies. Moving forward, analysis of large trial-based clinical samples; adherence to the highest methodological standards, and focus on validation analyses are necessary to identify clinically useful pharmacogenomic biomarkers of outcome.     

The prohibitin 3' untranslated region polymorphism in patients with ovarian cancer

OBJECTIVE: Prohibitin is an important antiproliferative protein inhibiting cell proliferation by blocking the G1/S transition of the cell cycle. Recent findings indicate that the presence of at least one mutant allele within a certain prohibitin gene polymorphism causes inactivation of bioactive RNA resulting in the loss of its pro-apoptotic function and a subsequent risk for malignant growth. Based on these findings we studied whether the presence of this prohibitin polymorphism increases the risk and worsens the prognosis of ovarian cancer in Caucasian women. STUDY DESIGN: A polymorphism within the 3' untranslated region (UTR) of the prohibitin gene was evaluated by pyrosequencing in 136 Caucasian patients with epithelial ovarian cancer and 129 healthy Caucasian controls. RESULTS: The wild-type C/C, heterozygous C/T, and the mutant T/T prohibitin genotype was found in 88 (64.7%), 46 (33.8%), and 2 (1.5%) patients with ovarian cancer and in 84 (65.1%), 39 (30.2%), and 6 (4.7%) healthy controls. Presence of at least one mutant allele of the prohibitin 3' UTR polymorphism was not associated with an increased risk of ovarian cancer as compared to healthy controls (P=0.9). No association was found between presence of the prohibitin 3' UTR polymorphism and the clinico-pathological parameters tumor stage, tumor grade, and patients' age at diagnosis. Presence of at least one mutant allele of the prohibitin 3' UTR polymorphism was not associated with disease-free and overall survival. CONCLUSION: The prohibitin 3' UTR polymorphism was not associated with risk and prognosis of ovarian cancer in Caucasian women.     

Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations

Although gynecologic cancers account for only 10% of all new cancer cases in women, these cancers account for 20% of all female cancer survivors. Improvements in cancer care have resulted in almost 10 million cancer survivors, and this number is expected to grow. Therefore, determining the most cost-effective clinical surveillance for detection of recurrence is critical. Unfortunately, there has been a paucity of research in what are the most cost-effective strategies for surveillance once patients have achieved a complete response. Currently, most recommendations are based on retrospective studies and expert opinion. Taking a thorough history, performing a thorough examination, and educating cancer survivors about concerning symptoms is the most effective method for the detection of most gynecologic cancer recurrences. There is very little evidence that routine cytologic procedures or imaging improves the ability to detect gynecologic cancer recurrence at a stage that will impact cure or response rates to salvage therapy. This article will review the most recent data on surveillance for gynecologic cancer recurrence in women who have had a complete response to primary cancer therapy.     

Investigation of resistin 420 and 62 gene polymorphism in patients with endometrial cancer

Objective

We aimed to assess resistin gene polymorphisms, namely 420C > G and 62G > A and their effect on the risk of endometrial cancer (EC).

A polymorphism in the matrix metalloproteinase-1 gene promoter is associated with the prognosis of patients with ovarian cancer

OBJECTIVE: The enzyme matrix metalloproteinase (MMP)-1 is involved in ovarian carcinogenesis. A common guanine insertion-deletion promoter polymorphism within the gene encoding MMP-1 (MMP1) has been suggested to be a candidate gene for ovarian cancer. We investigated whether this common polymorphism can also serve as independent prognostic parameter in a large series of affected women. METHODS: The MMP1 promoter polymorphism was examined in 151 Caucasian patients with epithelial ovarian cancer using polymerase chain reaction. Results were correlated with clinical data. RESULTS: No associations were ascertained between the MMP1 polymorphism and tumor stage (P = 1.0, odds ratio [OR] 1.08), lymph node involvement (P = 1.0, OR 0.8), tumor grading (P = 0.2, OR 0.5), and patient's age at diagnosis (P = 1.0, OR 1.04). Besides the clinically established prognosticators, tumor stage and histological grade, presence of the MMP1 polymorphism was associated with a shortened disease-free and overall survival in a univariate Kaplan-Meier analysis (P = 0.01) and a multivariate Cox regression model (P = 0.04). CONCLUSION: Presence of the MMP1 gene promoter polymorphisms was found to be a negative prognostic parameter in patients with ovarian cancer.     

NUCB2 gene polymorphism and its relationship with nesfatin-1 levels in polycystic ovary syndrome

Nesfatin-1, encoded by the nucleobindin-2 (NUCB2) gene, is an anorexigenic protein related to energy metabolism, obesity, and insulin resistance. The aim of this study was to evaluate NUCB2 gene polymorphism (rs757081) and its association with serum levels of nesfatin-1 in obese and non-obese women with polycystic ovary syndrome (PCOS). In the study population, we analyzed 60 patients with PCOS and 26 age-matched healthy women as controls. The patients with PCOS were divided into two groups based on body mass index (BMI): obese group (n?=?28) or non-obese group (n?=?32). NUCB2 was genotyped using the polymerase chain reaction-restriction (PCR) technique. Serum nesfatin-1 level was measured by enzyme-linked immunosorbent assay (ELISA). Nesfatin-1 levels in the obese PCOS group were significantly lower than those in the non-obese PCOS and control groups (p?p?>?0.05), whereas nesfatin-1 levels in the CC and CG genotypes were lower than those in the GG genotype. Nesfatin-1 decreases in PCOS, especially in obese women, and is negatively correlated with cardiometabolic risk factors. Although genotype disturbances of NUCB2 were similar among the groups, CC and CG genotypes accompanied lower nesfatin-1 levels. C allele of NUCB2 gene polymorphism and nesfatin-1 may play a role in the pathophysiology of PCOS.     

CYP17 genetic polymorphism in patients with endometrial hyperplasia and cancer

Abstract.   Aban M, Arslan M, Tok E, Tekes S, Budak T, Altintas A. CYP17 genetic polymorphism in patients with endometrial hyperplasia and cancer. Int J Gynecol Cancer 2006; 16(Suppl. 1): 448–451.
We investigated the association of CYP17 gene polymorphism with the risk of having endometrial cancer and a well-known precursor of it, endometrial hyperplasia. Group A (control group) consisted of 35 patients who had histologically proven normal endometrium. Group B and C consisted of 18 and 30 patients who had endometrial hyperplasia with and without atypia, respectively. Group D consisted of 57 patients who had endometrial cancer. Venous blood samples were collected from patients in groups, and polymerase chain reaction was performed to determine the CYP17 gene polymorphism. Significant increase of A1/A1 and a decrease of A1/A2 genotype frequencies have been determined in patients with endometrial cancer and with atypical endometrial hyperplasia. No significant differences were found between groups in the frequency of A2/A2 genotype. There was no significant difference between the groups in the meaning of allele distributions. CYP17 polymorphism had correlation with endometrial atypia and cancer. Related effects of different types of CYP17 gene variants on the progression of hyperplastic endometrial cells into carcinoma should be evaluated in further studies. Progress in this area would help us modulate preventive treatments used in those actual high–risk group patients.     

Low serum T3 levels are associated with false-positive results when using the risk of ovarian malignancy algorithm (ROMA) in women with benign ovarian disease

ObjectiveWe investigated factors that could cause false-positive results when using the risk of ovarian malignancy algorithm (ROMA) for assessing ovarian cancer risk.Materials and methodsROMA scores were calculated from patients followed surgery to remove a pelvic mass. We compared a false-positive group with a true-negative group of ROMA scores.ResultsWe analyzed 324 patients using medical records. There were 22 with an epithelial ovarian cancer (EOC), 15 with a borderline ovarian tumor, and 287 with benign disease. Twenty-nine (10.1%) of the patients with benign disease showed high-risk ROMA score (false positive) and 13/37 (35%) patients with EOC, or borderline ovarian tumor showed low ROMA scores (false negatives). The median serum triiodothyronine (T3) level of the false-positive ROMA group in patients with benign disease was lower than in the true-negative ROMA group (p < 0.001) and the estimated glomerular filtration rate (eGFR) was also lower (p = 0.001) in the false-positive ROMA group. Median serum T3 levels in the true-positive ROMA group among patients with EOC, or borderline ovarian tumor were lower than in the false-negative ROMA group (p = 0.043).ConclusionMedian serum T3 level and eGFR in the false-positive ROMA group in patients with benign ovarian disease were lower than in the true-negative group.